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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 19 recordsLinked to original sources
PubMed1992

The role of non-steroidal anti-inflammatory drugs in acute liver injury.

OBJECTIVE: To investigate the association between use of non-steroidal anti-inflammatory drugs and serious, acute non-infectious liver injury. DESIGN: Retrospective cohort study, cross over design. SETTING: Health records from provincial database in Saskatchewan, Canada, 1982-6. SUBJECTS: 228,392 adults who contributed 645,456 person years. All were either using or had used non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Number and type of prescriptions for non-steroidal anti-inflammatory drugs. Admission to hospital for newly diagnosed acute liver injury. RESULTS: There were 34 admissions to hospital; 16 among subjects currently using non-steroidal anti-inflammatory drugs and 18 among subjects who were not. The incidence rate among current users was 9 per 100,000 person years (95% confidence interval 6 to 15 per 100,000 person years). Subjects currently using non-steroidal anti-inflammatory drugs had twice the risk of newly diagnosed liver injury as those not currently taking these drugs (rate ratio 2.3; 95% confidence interval 1.1 to 4.9) and an excess risk of 5 per 100,000 person years. The age and sex adjusted risk ratio was 1.7 (0.8 to 3.7). The strength of the association increased when only cases with no concomitant use of other hepatotoxic drugs were considered (4.0; 0.9 to 19.0). The rate ratio for people having received one to nine prescriptions was constant. There was no increased risk with long duration of treatment (1.0; 0.3 to 3.5). CONCLUSIONS: There is a small excess risk of serious, acute non-infectious liver injury associated with the use of non-steroidal anti-inflammatory drugs.

Acute Disease↗
PubMed1992

Aspects of medical history and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands.

During 1984-88 a population-based case-control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. We observed an inverse relationship between medical treatment for allergy-related conditions and the development of pancreatic cancer (30 cases vs. 130 controls, OR 0.57, 95% CI 0.36 to 0.90). A history of gallbladder problems, gallstones, cholecystectomy, stomach or duodenal ulcer, pancreatitis, appendicitis, diabetes or tonsillectomy was not related to risk. In direct responses, compared with once daily, a positive relationship was seen for stool frequency, 10 years ago, of less than once daily (18 cases vs. 40 controls, OR 2.10, 95% CI 1.09 to 4.04). In men, diabetes treated with insulin and diagnosed more than 1 year previously was significantly and positively related to risk (5 cases vs. 1 control, OR 11.66, 95% 1.28 to 105.95). In brief, the results of the present study suggest that a history of allergy-related conditions may protect, whereas a past stool frequency of less than once daily may enhance the risk of cancer of the pancreas. Other elements of the medical history were not consistently related to risk.

Adult↗
PubMed1992

Anthropometric and reproductive variables and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands.

During 1984-88 a population-based case-control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. In women, a significant, positive dose-response effect of height was seen (p-value trend less than 0.005). Compared with ages 14 or more, women with an early age at menarche, i.e., 11 years or less, had a 3-fold increase in risk (15 cases vs. 23 controls, OR 3.07, 95% CI 1.35 to 7.00). Other apsects of the reproductive history were not related to risk. In brief, the results of the present study support the hypothesis that, in women, early menarche and greater adult stature may be early predictors of the development of cancer of the pancreas later in life.

Adult↗
PubMed1992

K-current mediation of prolactin-induced proliferation of malignant (Nb2) lymphocytes.

The effects of different concentrations of various K-current blockers on prolactin-induced proliferation and membrane K-currents in malignant lymphocytes (Nb2 cells) were investigated. Membrane currents were measured with the whole cell patch-clamp technique, and lymphocyte density was quantified by both spectrophotometric and conventional methods. K-current blockers tested (quinidine, 4-aminopyridine, barium, and tetraethylammonium) exhibited similar rank order potency for K-current block and inhibition of prolactin-induced proliferation of malignant lymphocytes. Because Nb2 cells proliferate independently of a transmembrane Ca-influx, these results suggest that K-currents per se rather than K-current modulation of Ca-influx is an essential event for lymphocyte proliferation.

4-Aminopyridine↗
PubMed1992

High-frequency oscillatory ventilation compared with conventional mechanical ventilation in newborn lambs: effects of increasing airway pressure on intracranial pressures.

We tested the hypothesis that intracranial pressures and cerebral perfusion pressure in the newborn are more seriously affected by increasing airway pressure during high-frequency oscillatory ventilation (HFOV) than during conventional mechanical ventilation (CMV). Mean airway pressure was acutely elevated in stepwise fashion to 25 cm H2O in six anesthetized, paralyzed newborn lambs. Pressure (mean +/- SE) increased similarly during HFOV and CMV in the jugular vein (7 +/- 1 and 8 +/- 1 cm H2O, respectively), the sagittal sinus (6 +/- 1 and 7 +/- 1 cm H2O), and the cerebrospinal fluid of the lateral ventricle (4 +/- 1 and 6 +/- 1 cm H2O). Decreases in arterial blood pressure (-13 +/- 2 and -10 +/- 2 cm H2O) and cerebral perfusion pressure (-17 +/- 2 and -16 +/- 2 cm H2O) were also similar during HFOV and CMV. Intracranial pressure-volume curves were generated by incrementing cerebrospinal fluid volume in eight lambs. Curves generated during HFOV and CMV were similar, reflecting a similar intracranial compliance during the two ventilatory modes. These data indicate that intracranial compliance and the effects of increasing airway pressure upon intracranial pressures are not significantly different between HFOV and CMV.

Air Pressure↗
PubMed1992

Effects of external constraint on the fetal left ventricular function curve.

To determine if external ventricular constraint significantly limits fetal left ventricular (LV) stroke volume and can thus account for the plateau of the fetal ventricular function curve, we studied nine fetal lambs (142 to 144 days' gestation) after partial delivery by cesarean section (halothane anesthetic). LV stroke volume (electromagnetic flow probe), LV end-diastolic pressure, and external ventricular constraint (intrapericardial pressure [liquid-filled balloon]) were measured over a range of end-diastolic pressures under two conditions: with a closed chest and closed pericardium and with an open chest and open pericardium. Stroke volume recorded during open chest and open pericardium exceeded those recorded during closed chest and closed pericardium at any given end-diastolic pressure (p less than 0.01). Decreases in external ventricular constraint significantly increased LV transmural pressure (preload) and substantially increased fetal LV stroke volume. Thus the plateau of the fetal ventricular function curve was largely a result of external ventricular constraint limiting LV preload, not necessarily a result of myocyte immaturity.

Animals↗
PubMed1992

Oral contraceptive type and functional ovarian cysts.

OBJECTIVE: We tested the hypothesis that multiphasic, low-dose monophasic, and high-dose monophasic oral contraceptives share a common protective effect against functional ovarian cysts. STUDY DESIGN: We conducted a cohort study using the automatic files of Maine Medicaid to assemble a population of 7462 women between the ages of 15 and 44 who were prescribed an oral contraceptive between Jan. 1, 1987, and Dec. 31, 1988. We included as cases 32 women with a principal diagnosis of a functional ovarian cyst confirmed by medical records as being greater than 20 mm in diameter. RESULTS: At comparison with the absence of an oral contraceptive prescription, we observed decreasing rates of functional ovarian cysts among women prescribed multiphasic pills (rate ratio 0.91, 95% confidence interval 0.3000 to 2.31), low-dose monophasic pills with less than or equal to 35 micrograms estrogen (rate ratio 0.52, 95% confidence interval 0.17 to 1.33), and high-dose monophasic pills with greater than 35 micrograms estrogen (rate ratio 0.24, 95% confidence interval 0.01 to 1.34). CONCLUSIONS: The protective effect of oral contraceptives against functional ovarian cysts reported previously for high-dose monophasic pills may be attenuated with newer pills of lower hormonal potency.

Adolescent↗
PubMed1992

Patterns of interchange in the dispensing of non-steroidal anti-inflammatory drugs.

Patterns of change in dispensings of non-steroidal anti-inflammatory drugs (NSAID) were evaluated from the pharmacy records of a health maintenance organization (HMO). Overall, 52.8% of NSAID prescriptions were followed by another NSAID prescription within 60 days. Among patients for whom NSAIDs were dispensed twice within 60 days, 15% received a different NSAID. Switching between NSAIDs was more frequent in younger age groups; there was no difference between males and females. Chronic and non-chronic indications for NSAID use were associated with similar probabilities of switches between drugs among repeat users. NSAIDs that were frequently switched to for lack of efficacy or for prior toxicity of other NSAIDs were not as a whole themselves associated with more frequent switches for the same reasons.

Adolescent↗
PubMed1992

Beta-thalassemia intermedia with exceptionally high hemoglobin A2: relationship to mutations in the beta-gene promoter.

Small deletions of the 5' portion of the beta-globin gene that remove the promoters but stop 3' to the delta-globin gene are recognized as the sole cause of beta-thalassemia with exceptionally high hemoglobin A2 (HbA2) levels. Two patients with beta-thalassemia intermedia and exceptionally high levels of HbA2 (10.4 and 12.0%) were examined. One patient was a combined heterozygote for the -88 C----T and a novel -87 C----A mutation, while the other was homozygous for the -29 A----G beta(+)-thalassemia mutation. The remainder of the beta genes were normal. There was no evidence for deletions involving the 5' portion of the beta gene or the region between the beta and delta genes. Gene mapping studies excluded the possibility of a beta delta-anti-Lepore hemoglobin gene with beta promoters and delta coding sequences. There were no mutations in the promoters of the G gamma or A gamma-globin genes that have been associated with the hereditary persistence of HbF phenotype. The delta-globin gene promoters were normal from codon 17 to position -145 relative to the mRNA capping site. There appears to be considerable heterogeneity of HbA2 and HbF levels in patients who are homozygous or mixed heterozygotes for mutations in the TATA box and other promoter elements of the beta-globin gene. The capacity for proteolysis within the erythrocyte may vary among individuals. The authors hypothesize that in the exceptionally high HbA2 beta-thalassemia intermedia phenotype, proteolysis of superfluous alpha-globin chains is less efficient than in patients with customary levels of HbA2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Nonsteroidal antiinflammatory drugs and gastrointestinal hospitalizations in Saskatchewan: a cohort study.

We evaluated the association between individual nonsteroidal antiinflammatory drugs (NSAIDs) and gastrointestinal (GI) toxicity in a retrospective cohort study aimed at examining and comparing the incidence of serious gastrointestinal disorders among NSAIDs users. We observed 2,302 GI hospitalizations among diclofenac, indomethacin, naproxen, piroxicam, sulindac, and other NSAIDs users in the province of Saskatchewan, Canada, from 1982 to 1986 for 228,392 persons who contributed 679,075 person-years of follow-up and filled close to 1.5 million NSAID prescriptions. Current NSAID users presented an increased risk of GI hospitalization [rate ratio (RR) = 3.9, 95% confidence interval = 3.5-4.4]. RRs decreased as time since the last prescription increased: 2.2 (1.9-2.6) for recent past users and 1.3 (1.1-1.5) for less recent past users. Among current users, RRs were the highest in indomethacin users (5.1, 4.3-6.0), and the lowest in sulindac users (3.1, 2.3-4.2). All of these results are adjusted for calendar time, sex, and age. Age showed a particularly strong association with the risk of GI hospitalization.

Adolescent↗
PubMed1992

Effect of fetal haemoglobin on the accuracy of pulse oximetry in preterm infants.

Pulse oximeters are programmed with a calibration curve derived from studies done in adults. Whether fetal haemoglobin levels affect their reliability is unclear. This study reports the accuracy of pulse oximetry in 22 preterm infants (mean 31 weeks, range 25-36 weeks gestation) between 1 h and 73 days of age. Oxygen saturation obtained from a Nellcor N-200 pulse oximeter (SpO2) was compared with simultaneous arterial values (functional SaO2) measured by a Radiometer OSM3 Hemoximeter over a SpO2 range of 83-99%. Fetal haemoglobin (HbF), carboxyhaemoglobin (HbCO) and methaemoglobin (HbMet) measured by the hemoximeter ranged between 0-100%, 0-3.5% and 0-0.8% respectively. Linear regression analysis revealed a close correlation between SpO2 and functional SaO2 (SpO2 = 0.75 SaO2 + 24.43, r = 0.88, P less than 0.001) over a wide range of values for PCV, heart rate, blood pressure, PaO2, PaCO2 and pH. The mean SpO2-SaO2 difference of 1.3, (s.d. 2.5%, P less than 0.001) was unaffected by HgF, HbCO or HbMet but was increased in infants receiving inotropic support. We conclude that the Nellcor N-200 pulse oximeter gives reliable oxygen saturation measurements unaffected by the HbF level in preterm infants.

Fetal Hemoglobin↗
PubMed1992

In vitro glucoregulation of prolactin secretion.

In this study we have examined the direct glucoregulation of prolactin secretion from normal anterior pituitary cells in vitro and have found that changes in medium glucose concentration regulate the amount of prolactin released. Nature and/or degree of this response to glucose was influenced by some effect, long-lived in vitro, which was correlatable to serum insulin levels. When the cells were derived from animals with mean low-normal serum insulin levels, there was a stimulation of prolactin secretion by hypoglycemia, the response was rapid, transient, dose-dependent, and could be duplicated by 2-deoxyglucose. When the cells were derived from animals with a higher mean serum insulin level, the prolactin secretion from the cells was slowly, adversely affected by hypoglycemia. Conversely, elevated glucose caused a depression in prolactin secretion in the first group and a stimulation of prolactin secretion in the second. We conclude (1) that modulation of glucose levels in vitro regulates prolactin release from pituitary mammotrophs and (2) that this glucose regulation of prolactin release is in turn coregulated with or regulated by insulin.

Animals↗
PubMed1992

Changes in pericardial pressure during the perinatal period.

BACKGROUND: To determine how the tissues that surround the heart affect diastolic and systolic function during the perinatal period, we studied the pressure-diameter relation of the left ventricle in partially delivered fetal lambs. METHODS AND RESULTS: We anesthetized (1.5-2.0% halothane, balance O2) and ventilated six pregnant ewes (142-144 days of gestation) and then partially delivered each lamb by cesarean section. Each lamb was instrumented to record left ventricular anteroposterior diameters (endocardial ultrasonic transducers), pericardial pressure (liquid-containing balloon), and left ventricular pressure (transducer-tipped catheter). Left ventricular pressure-diameter relations were recorded under three conditions: initially, with a closed chest and closed pericardium (before ventilation); second, after interruption of the umbilical circulation and 1 hour of ventilation; and finally, when the lungs and the pericardium were retracted from the heart. Pericardial pressure (recorded at a common diameter, i.e., the maximal end-diastolic diameter recorded before ventilation) decreased by 48% after 1 hour of ventilation (p < 0.05). After ventilation, left ventricular anteroposterior diameters were 4-5% greater (p < 0.05) at each end-diastolic pressure compared (12.5, 15.0, 17.5, and 20 mm Hg). Thus, ventilation appeared to increase left ventricular diastolic compliance. Contractility also appeared to increase after ventilation when evaluated using ventricular stroke work as a function of end-diastolic pressure as preload. When we used a more appropriate measure of preload (i.e., transmural end-diastolic pressure), ventilation did not change left ventricular diastolic compliance or contractility. Thus, left ventricular systolic function increased because of an increase in preload. CONCLUSIONS: The tissues surrounding the fetal heart significantly augment pericardial pressure and limit left ventricular preload. The initiation of ventilation reduces pericardial pressure, increases left ventricular preload, and increases left ventricular systolic function. At birth, a decrease in pericardial pressure and the resulting increase in preload may help increase left ventricular output through the Frank-Starling mechanism.

Animals↗
PubMed1992

Indirect relation between rises in oxygen consumption and left ventricular output at birth in lambs.

To examine the relation between increased newborn oxygen requirements and the postnatal rise in cardiac output, we measured left ventricular (LV) output, organ blood flows, and whole-body oxygen consumption using radioactive microspheres in late-gestation sheep fetuses and in the same animals 1 and 4 hours after cesarean section delivery. LV output rose from 264 +/- 23 ml.min-1.kg body wt-1 in fetuses to 444 +/- 33 ml.min-1.kg body wt-1 in lambs at 1 hour after delivery (p less than 0.005) and was unchanged at 4 hours after delivery. This rise in LV output was associated with a more than fourfold increase in the LV flow contribution to tissues situated distal to the ductus arteriosus (fetus, 51 +/- 9 ml.min-1.kg body wt-1; lamb, 226 +/- 22 ml.min-1.kg body wt-1; p less than 0.005), which were mainly perfused by the right ventricle in utero. However, average blood flow to body tissues was similar in fetuses (37 +/- 4 ml.min-1.100 g tissue-1), 1-hour lambs (39 +/- 4 ml.min-1.100 g tissue-1), and 4-hour lambs (40 +/- 5 ml.min-1.100 g tissue-1). Oxygen consumption increased by 58%, from 7.84 +/- 0.43 ml.min-1.kg body wt-1 in fetuses to 12.38 +/- 2.4 ml.min-1.kg body wt-1 in 1-hour lambs (p less than 0.01), and was unchanged in 4-hour lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prolactin isoform 2 as an autocrine growth factor for GH3 cells.

Because PRL has growth factor activities in several tissues, we have asked whether it also has autocrine growth factor activity in pituitary GH3 cells. GH3 cells were grown at increasing densities in the presence or absence of antirat PRL (polyclonal and monoclonal) or nonspecific antibodies. Cell proliferation increased with increasing cell density, as did the concentration of PRL in the medium. Antirat PRL, but not control antibody, markedly inhibited but did not eliminate cell proliferation, and this effect was diminished with increasing PRL concentration in the medium. PRL receptors were demonstrated on 40-50% of the cells by indirect immunofluorescence using a specific antirat PRL receptor monoclonal antibody. Cell surface PRL was colocalized to the same 40-50% of the cells and copatched or cocapped along with the receptors. Absence or presence of PRL receptors did not correlate with stage of the cell cycle, as judged by ethidium bromide dual labeling. Cell surface PRL was found to be on PRL-containing cells. These data have fulfilled four criteria necessary for establishment of a substance as a secreted autocrine growth factor: 1) the factor must be secreted; 2) in log growth phase, increased cell proliferation should occur at increased cell densities; 3) the cells must display a receptor for the factor; and 4) there must be a growth response to the factor. Thus we have established that PRL is an autocrine growth factor for at least 40-50% of the GH3 cell population. This, to our knowledge, is the first example of autocrine growth factor activity of a major hormone normotopically expressed.

Animals↗